Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Mar 17;188(1):178-94.
doi: 10.1016/j.bbr.2007.10.029. Epub 2007 Nov 4.

Development of a mouse test for repetitive, restricted behaviors: relevance to autism

Sheryl S Moy  1 , Jessica J Nadler, Michele D Poe, Randal J Nonneman, Nancy B Young, Beverly H Koller, Jacqueline N Crawley, Gary E Duncan, James W Bodfish
Affiliations

Development of a mouse test for repetitive, restricted behaviors: relevance to autism

Sheryl S Moy et al. Behav Brain Res. .

Abstract

Repetitive behavior, a core symptom of autism, encompasses stereotyped responses, restricted interests, and resistance to change. These studies investigated whether different components of the repetitive behavior domain could be modeled in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J, BALB/cByJ, BTBR T+tf/J, and FVB/NJ, and mice with reduced expression of Grin1, leading to NMDA receptor hypofunction (NR1neo/neo mice), were tested for exploration and preference for olfactory stimuli in an activity chamber with a 16-hole floor-board. Reduced exploration and high preference for holes located in the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All inbred strains had initial high preference for a familiar olfactory stimulus (clean cage bedding). BTBR T+tf/J was the only strain that did not demonstrate a shift in hole preference towards an appetitive olfactory stimulus (cereal or a chocolate chip), following home cage exposure to the food. The NR1neo/neo mice showed lower hole selectivity and aberrant olfactory stimulus preference, in comparison to wildtype controls. The results indicate that NR1neo/neo mice have repetitive nose poke responses that are less modified by environmental contingencies than responses in wildtype mice. 25-30% of NMDA receptor hypomorphic mice also show self-injurious responses. Findings from the olfactory studies suggest that resistance to change and restricted interests might be modeled in mice by a failure to alter patterns of hole preference following familiarization with an appetitive stimulus, and by high preference persistently demonstrated for one particular olfactory stimulus. Further work is required to determine the characteristics of optimal mouse social stimuli in the olfactory hole-board test.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic of hole-board numbering system in the activity chamber, indicating four corner holes (1, 4, 13, and 16), eight wall holes (2, 3, 5, 8, 9, 12, 14, and 15), and four center holes (6, 7, 10, and 11).
Figure 2
Figure 2
Hole preference during a one-hour exploration test in C57BL/6J (B6; young, 8-9 weeks in age), B6 and BALB/cByJ (BALB; 7 months in age) male mice. Criterion levels for preference were 12.5% (High), 6.25% (Average; equal distribution across holes), and 3.125% (Low). Mean total number of nose pokes for data in each panel were: B6 (young) A, 212.5 (SEM=27.0), B, 178.3 (SEM=11.8), B6 C, 94.3 (SEM=14.9), D, 66.8 (SEM=7.6), and BALB E, 25.4 (SEM=7.2), and F, 23.1 (SEM=4.8).
Figure 3
Figure 3
Number of nose pokes during a one-hour exploration test in B6 (young, 8-9 weeks in age), B6 and BALB (7 months in age) male mice. Data shown are means (+SEM). * p< 0.05, within-group comparison to nose poke counts for center holes.
Figure 4
Figure 4
Hole preference during a one-hour exploration test in B6, BTBR T+tf/J (BTBR), and FVB/NJ (FVB) male mice. Criterion levels for preference were 12.5% (High), 6.25% (Average; equal distribution across holes), and 3.125% (Low). Mean total number of nose pokes for data in each panel were: B6 A, 222.4 (SEM=25.0), B, 107.8 (SEM=16.1), BTBR C, 107.8 (SEM=13.2), D, 55.2 (SEM=8.9), and FVB E, 158.5 (SEM=8.7), and F, 121.9 (SEM=7.9).
Figure 5
Figure 5
Number of nose pokes during a one-hour exploration test in B6, BTBR, and FVB male mice. Data shown are means (+SEM). * p< 0.05, within-strain comparison to nose poke counts for center holes.
Figure 6
Figure 6
Hole preference during a 1-hour exploration test in NR1 NMDA receptor-hypomorphic mice. Criterion levels for preference were 12.5% (High), 6.25% (Average; equal distribution across holes), and 3.125% (Low). Mean total nose pokes per subject: NR1+/+, 49.9 (SEM=9.8), NR1neo/neo, 82.3 (SEM=22.8).
Figure 7
Figure 7
Numbers of nose pokes during hole-board exploration in NR1 NMDA receptor-hypomorphic mice. Data shown are means (+SEM). * p< 0.05, within-genotype comparison to nose poke counts for center holes.
Figure 8
Figure 8
Total distance traveled during hole-board exploration. Data shown are means (+SEM) for a 1-hour test. Inbred strains were 6-9 weeks in age for exploration test, except for one group of B6 and one group of BALB, which were 7 months of age. NR1 mice were 3-5 months in age. *p<0.05, different from adjacent group; **p<0.05; different from both adjacent groups (black-filled bars).
Figure 9
Figure 9
Hole preference in a 1-hour olfactory stimuli test. Center holes were empty (E), or contained familiar, clean cage bedding (B), a gauze square with 0.05 ml dilute lemon extract (L), or a novel cinnamon cereal (CR). Criterion levels for preference were 18.75% (Extreme), 12.5% (High), 6.25% (Average; equal distribution across holes), and 3.125% (Low). Mean total number of nose pokes per subject: B6 (young), 106.1 (SEM=10.8), B6, 95.1 (SEM=13.9), BALB, 25 (SEM=4.2).
Figure 10
Figure 10
Percent of total nose pokes toward the four center holes (A) before and (B) after familiarization with cereal (first three groups) or chocolate chips (last three groups). Criterion levels for preference were 18.75% (Extreme), 12.5% (High), 6.25% (Average; equal distribution across holes), and 3.125% (Low).
Figure 11
Figure 11
Number of nose pokes into center holes (A) before and (B) after familiarization with cereal (first three groups) or chocolate chips (last three groups). Data shown are means (+SEM). * p< 0.05, within-group comparison to nose poke counts for hole containing familiar cage bedding. # p<0.05, within-group comparison to nose poke counts for hole containing familiar cereal or familiar chocolate chip.
Figure 12
Figure 12
Familiarization with a chocolate chip in NR1 NMDA receptor-deficient mice. Criterion levels for preference were 18.75% (Extreme), 12.5% (High), 6.25% (Average; equal distribution across holes), and 3.125% (Low). Data shown in B are means (+SEM). * p< 0.05, within-genotype comparison to nose poke counts for hole containing familiar cage bedding. # p<0.05, within-genotype comparison to nose poke counts for hole containing familiar chocolate chip.
Figure 13
Figure 13
Time in the center of the activity chamber during a hole-board test for general exploration, and during a hole-board test with olfactory stimuli, following familiarization to the appetitive stimulus. Data shown are means (+ SEM) for one-hour tests. Inbred strains were 6-9 weeks in age for exploration test, except for one group of B6 and one group of BALB, which were 7 months of age. NR1 mice were 3-4 months in age. * p<0.05, within-group comparison.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alexander AL, Lee JE, Lazar M, Boudos R, Dubray MB, Oakes TR, Miller JN, Lu J, Jeong EK, McMahon WM, Bigler ED, Lainhart JE. Diffusion tensor imaging of the corpus callosum in Autism. Neuroimage. 2007;34:61–73. - PubMed
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) American Psychiatric Publishing, Inc; Washington, DC: 2000.
    1. Amico JA, Vollmer RR, Cai HM, Miedlar JA, Rinaman L. Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. Am J Physiol Regul Integr Comp Physiol. 2005;289:R1798–1806. - PubMed
    1. Asaka Y, Jugloff DG, Zhang L, Eubanks JH, Fitzsimonds RM. Hippocampal synaptic plasticity is impaired in the Mecp 2-null mouse model of Rett syndrome. Neurobiol Dis. 2006;21:217–227. - PubMed
    1. Aylward EH, Minshew NJ, Goldstein G, Honeycutt NA, Augustine AM, Yates KO, Barta PE, Pearlson GD. MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology. 1999;53:2145–2150. - PubMed

Publication types

MeSH terms